Cancer Causes & Control

, Volume 23, Issue 12, pp 1995–2002 | Cite as

Tobacco consumption and genetic susceptibility to nasopharyngeal carcinoma (NPC) in Thailand

  • Jajah Fachiroh
  • Suleeporn Sangrajrang
  • Mattias Johansson
  • Hélène Renard
  • Valérie Gaborieau
  • Amélie Chabrier
  • Somjin Chindavijak
  • Paul Brennan
  • James D. McKayEmail author
Original paper



The incidence of nasopharyngeal carcinoma (NPC) varies substantially worldwide, with an endemic pocket in Southeast Asia.


We assessed lifestyle and genetic factors in relation to NPC risk among 681 NPC cases and 1,078 controls from Thailand. Evaluated lifestyle factors included traditionally preserved foods, tobacco smoking, betel quid chewing, and alcohol consumption. Genetic factors included six variants implicated in a previous a genome-wide association study (GWAS) of NPC and three variants residing near the CHRNA3 and TERT genes that were linked to lung cancer risk in Asian populations. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated using unconditional logistic regression.


Frequent consumption of fermented vegetables was associated with increased NPC risk (OR of consumption ≥weekly vs. ≤rare 1.78, 95 % CI 1.24–2.55, p trend = 0.005), as was tobacco smoking (p trend < 0.001), former and current smokers displaying OR of 1.57 (95 % CI 1.10–2.30) and 2.00 (95 % CI 1.48–2.71) compared to never smokers, respectively. Four out of six genetic variants implicated in the recent NPC GWAS were associated with NPC risk (p trend ≤ 0.03), as well as two variants (rs402710 and rs2736098) on the TERT locus at 5p15.33 (p = 0.004 and p = 0.04, respectively).


These results strengthen our previous observation that tobacco smoking is an important risk factor of NPC in this population. Four out of six genetic variants identified in a recent NPC GWAS were confirmed, and the association noted with variants on 5p15.33 suggests that this locus is involved in NPC susceptibility, representing a novel finding in NPC epidemiology.


Nasopharyngeal carcinoma (NPC) Thailand Tobacco smoking Genetic Genotyping 



We are grateful to all subjects who participate in this study and field staffs for all the effort to collect the information. We would also like to thank Kevin Urayama for critically reading the manuscript and giving constructive suggestions. The work reported in this paper was undertaken during the tenure of a Postdoctoral Fellowship from the International Agency for Research on Cancer (IARC) (for Jajah Fachiroh).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Lee A, Foo W, Mang O, Sze W, Chappell R, Lau W, Ko W (2003) Changing epidemiology of nasopharyngeal carcinoma in Hong Kong over a 20-year period (1980–1999): an encouraging reduction in both incidence and mortality. Int J Cancer 103(5):680–685PubMedCrossRefGoogle Scholar
  2. 2.
    Ji MF, Wang DK, Yu YL, Guo YQ, Liang JS, Cheng WM, Zong YS, Chan KH, Ng SP, Wei WI, Chua DT, Sham JS, Ng MH (2007) Sustained elevation of Epstein-Barr virus antibody levels preceding clinical onset of nasopharyngeal carcinoma. Br J Cancer 96(4):623–630PubMedCrossRefGoogle Scholar
  3. 3.
    Curado M, Edwards B, Shin H, Storm H, Ferlay J, Heanue M, Boyle P (2009) Cancer in five continents, vol IX. IARC, LyonGoogle Scholar
  4. 4.
    Devi BC, Pisani P, Tang TS, Parkin DM (2004) High incidence of nasopharyngeal carcinoma in native people of Sarawak, Borneo Island. Cancer Epidemiol Biomarkers Prev 13(3):482–486PubMedGoogle Scholar
  5. 5.
    IARC-Monograph (2009) A review of human carcinogens—Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol 10:1033–1034CrossRefGoogle Scholar
  6. 6.
    IARC-Monograph (2009) A review of human carcinogens—Part C: metals, arsenic, dusts, and fibres. Lancet Oncol 10:453–454CrossRefGoogle Scholar
  7. 7.
    IARC-Monograph (2009) A review of human carcinogens—Part B: biological agents. Lancet Oncol 10:321–322CrossRefGoogle Scholar
  8. 8.
    Hildesheim A, CP Wang (2012) Genetic predisposition factors and nasopharyngeal carcinoma risk: A review of epidemiological association studies, 2000–2011. Rosetta Stone for NPC: viral infection, and other environmental factors. Semin Cancer Biol 22:107–116Google Scholar
  9. 9.
    Bei J, Li Y, Jia W, Feng B, Zhou G, Chen L, Feng Q, Low H, Zhang H, He F, Tai E, Kang T, Liu E, Liu J, Zeng Y (2010) A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci. Nat Genet 42(7):599–603PubMedCrossRefGoogle Scholar
  10. 10.
    Khuhaprema T, Srivatanakul P, Attasara A, Sriplung H, Wiangnon S, Sumitsawan Y (2010) Cancer in Thailand. National Cancer Institute, BangkokGoogle Scholar
  11. 11.
    Ekburanawat W, Ekpanyaskul C, Brennan P, Kanka C, Tepsuwan K, Temiyastith S, Klinvimol T, Pongnikorn S, Sangrajrang S (2010) Evaluation of non-viral risk factors for nasopharyngeal carcinoma in Thailand: results from a case-control study. Asian Pac J Cancer Prev 11:929–932PubMedGoogle Scholar
  12. 12.
    McKay J, Hung R, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P et al (2008) Lung cancer susceptibility locus at 5p15.33. Nat Genet 40(12):1404–1406PubMedCrossRefGoogle Scholar
  13. 13.
    Truong T, Hung R, Amos C, Wu X, Bickeböller H, Rosenberger A, Sauter W, Illig T, Wichmann H, Risch A, Dienemann H, Kaaks R, Yang P et al (2010) Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the international lung cancer consortium. J Natl Cancer Inst 102(13):959–971PubMedCrossRefGoogle Scholar
  14. 14.
    Gallicchio L, Matanoski G, Tao XG, Chen L, Lam TK, Boyd K, Robinson KA, Balick L, Mickelson S, Caulfield LE, Herman JG, Guallar E, Alberg AJ (2006) Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review. Int J Cancer 119:1125–1135PubMedCrossRefGoogle Scholar
  15. 15.
    Jia W, Luo X, Feng B, Ruan H, Bei J, Liu W, Qian H, Feng Q, Chen L, Yao S, Zeng Y (2010) Traditional cantonese diet and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China. BMC Cancer 10:446–452PubMedCrossRefGoogle Scholar
  16. 16.
    Armstrong R, Imrey P, Lye M, Armstrong M, Yu M, Sani S (1998) Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary exposures. Int J Cancer 77:228–235PubMedCrossRefGoogle Scholar
  17. 17.
    West S, Hildesheim A, Dosemeci M (1993) Non-viral risk factors for nasopharyngeal carcinoma in the Philippines: results from a case-control study. Int J Cancer 55(5):722–777PubMedCrossRefGoogle Scholar
  18. 18.
    Ward M, Pan W, Cheng Y, Li F, Brinton L, Chen C, Hsu M, Chen I, Levine P, Yang C, Hildesheim A (2000) Dietary exposure to nitrite and nitrosamine and risk of nasopharyngeal carcinoma in Taiwan. Int J Cancer 86:603–609PubMedCrossRefGoogle Scholar
  19. 19.
    Brennan P, Bogillot O, Cordier S, Greiser E, Schill W, Vineis P, Lopez-Abente G, Tzonou A, Chang-Claude J, Bolm-Audorff U, Jöckel KH, Donato F, Serra C, Wahrendorf J, Hours M, T’Mannetje A, Kogevinas M, Boffetta P (2000) Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies. Int J Cancer 86 (2):289–294Google Scholar
  20. 20.
    Eby MT, Jasmin A, Kumar A, Sharma K, Chaudhary PM (2000) TAJ, a novel member of the tumor necrosis factor receptor family, activates the c-Jun N-terminal kinase pathway and mediates caspase-independent cell death. J Biol Chem 275:15336–15342PubMedCrossRefGoogle Scholar
  21. 21.
    Tsao SW, Tramoutanis G, Dawson CW, Lo AK, Huang DP (2002) The significance of LMP1 expression in nasopharyngeal carcinoma. Semin Cancer Biol 12(6):473–487PubMedCrossRefGoogle Scholar
  22. 22.
    Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y et al (2011) A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese. Nat Genet 43(8):792–796PubMedCrossRefGoogle Scholar
  23. 23.
    Métais JY, Dunbar CE (2008) The MDS1–EVI1 gene complex as a retrovirus integration site: impact on behavior of hematopoietic cells and implications for gene therapy. Mol Ther 16:439–449PubMedCrossRefGoogle Scholar
  24. 24.
    Wong TS, Tang KC, Kwong DL, Sham JS, Wei WI, Kwong YL, Yuen AP (2003) Differential gene methylation in undifferentiated nasopharyngeal carcinoma. Int J Oncol 22(4):869–874PubMedGoogle Scholar
  25. 25.
    Timofeeva MN, Hung RJ, Rafnar T, Christiani DC, Field JK, Bickeboller H, Risch A, McKay JD, Wang Y, Dai J, Gaborieau V, McLaughlin J, Brenner D, Narod S, Caporaso NE, Albanes D, Thun M, Eisen T, Wichmann HE, Rosenberger A, Han Y, Chen W, Zhu D, Spitz M, Wu X, Pande M, Zhao Y, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Krokan HE, Gabrielsen ME, Skorpen F, Vatten L, Njølstad I, Chen C, Goodman G, Lathrop M, Benhamou S, Vooder T, Välk K, Nelis M, Metspalu A, Raji O, Chen Y, Gosney J, Liloglou T, Muley T, Dienemann H, Thorleifsson G, Shen H, Stefansson K, Brennan P, Amos CI, Houlston R, Landi MT (2012) Influence of common genetic variation on lung cancer risk: meta-analysis of 14,900 cases and 29,485 controls. Hum Mol Genet [epub ahead of printing]Google Scholar
  26. 26.
    Chen H, Chen Y, Zhao Y, Fan W, Zhou K, Liu Y, Zhou L, Mao Y, Wei Q, Xu J, Lu D (2011) Association of sequence variants on chromosomes 20, 11, and 5 (20q13.33, 11q23.3, and 5p15.33) with glioma susceptibility in a Chinese population. Am J Epidemiol 173(8):915–922PubMedCrossRefGoogle Scholar
  27. 27.
    Chen X, Cai S, Chen Q, Ni Z, Tang J, Xu D, Wang X (2012) Multiple variants of TERT and CLPTM1L constitute risk factors for lung adenocarcinoma. Genet Mol Res 11(1):370–378PubMedCrossRefGoogle Scholar
  28. 28.
    Rafnar T, Sulem P, Stacey SN, Geller F, Gudmundsson J, Sigurdsson A, Jakobsdottir M, Helgadottir H, Thorlacius S, Aben KK, Blöndal T, Thorgeirsson TE, Thorleifsson G, Kristjansson K, Thorisdottir K, Ragnarsson R, Sigurgeirsson B, Skuladottir H, Gudbjartsson T, Isaksson HJ, Einarsson GV, Benediktsdottir KR, Agnarsson BA, Olafsson K, Salvarsdottir A, Bjarnason H, Asgeirsdottir M, Kristinsson KT, Matthiasdottir S, Sveinsdottir SG, Polidoro S, Höiom V, Botella-Estrada R, Hemminki K, Rudnai P, Bishop DT, Campagna M, Kellen E, Zeegers MP, de Verdier P, Ferrer A, Isla D, Vidal MJ, Andres R, Saez B, Juberias P, Banzo J, Navarrete S, Tres A, Kan D, Lindblom A, Gurzau E, Koppova K, de Vegt F, Schalken JA, van der Heijden HF, Smit HJ, Termeer RA, Oosterwijk E, van Hooij O, Nagore E, Porru S, Steineck G, Hansson J, Buntinx F, Catalona WJ, Matullo G, Vineis P, Kiltie AE, Mayordomo JI, Kumar R, Kiemeney LA, Frigge ML, Jonsson T, Saemundsson H, Barkardottir RB, Jonsson E, Jonsson S, Olafsson JH, Gulcher JR, Masson G, Gudbjartsson DF, Kong A, Thorsteinsdottir U, Stefansson K (2009) Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. Nat Genet 41(2):221–227Google Scholar
  29. 29.
    Jaworowska E, Trubicka J, Lener M, Masojć B, Złowocka-Perłowska E, McKay J, Renard H, Oszutowska D, Wokołorczyk D, Lubiński J, Grodzki T, Serwatowski P, Nej-Wołosiak K, Tołoczko-Grabarek A, Sikorski A, Słojewski M, Jakubowska A, Cybulski C, Lubiński J, Scott R (2011) Smoking related cancers and loci at chromosomes 15q25, 5p15, 6p22.1 and 6p21.33 in the Polish population. PLoS ONE 6(9):e25057PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Jajah Fachiroh
    • 1
    • 3
  • Suleeporn Sangrajrang
    • 2
  • Mattias Johansson
    • 3
  • Hélène Renard
    • 3
  • Valérie Gaborieau
    • 3
  • Amélie Chabrier
    • 4
  • Somjin Chindavijak
    • 2
  • Paul Brennan
    • 3
  • James D. McKay
    • 4
    Email author
  1. 1.Department of Histology and Cell Biology, Faculty of MedicineGadjah Mada UniversityYogyakartaIndonesia
  2. 2.National Cancer InstituteBangkokThailand
  3. 3.Genetic Epidemiology GroupInternational Agency for Research on Cancer (IARC)Lyon cedex 08France
  4. 4.Genetic Cancer Susceptibility GroupInternational Agency for Research on Cancer (IARC)Lyon cedex 08France

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